Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
In previous studies,researchers have used singing to treat respiratory function in patients with spinal cord injury.However,few studies have examined the way in which vocal training affects respiratory neural plastici...In previous studies,researchers have used singing to treat respiratory function in patients with spinal cord injury.However,few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury.Vocal respiratory training(VRT)is a type of vocal muscle-related treatment that is often a component of music therapy(MT)and focuses on strengthening respiratory muscles and improving lung function.In this randomized controlled study,we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury.Of an initial group of 37 patients,26 completed the music therapy intervention,which comprised five 30-minute sessions per week for 12 weeks.The intervention group(n=13)received VRT training delivered by professional certified music therapists.The control group(n=13)received respiratory physical therapy delivered by professional physical therapists.Compared with the control group,we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention.Further,the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification,with an increased number,path length,thickness,and density of nerve fiber bundles.These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2020-013-1)on April 1,2020,and was registered with the Chinese Clinical Trial Registry(registration No.Chi CTR2000037871)on September 2,2020.展开更多
Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and...Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.展开更多
Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the micros...Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T_（10） spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord（R = 0.919, P = 0.027）, white matter（R = 0.932, P = 0.021）, and gray matter（R = 0.882, P = 0.048）. Additionally, the other parameters had almost no correlation with the score（P 〉 0.05）. In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.展开更多
Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled tri...Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury.Among 31 included patients with spinal cord injury,18 completed the treatment.These 18 patients were randomly assigned to undergo music therapy(intervention group,30 min/d,5 times a week,for a total of 12 weeks;n=9,7 males and 2 females;30.33±11.74 years old)or normal respiratory training(control group,n=9;8 males and 1 female;34.78±11.13 years old).Both patient groups received routine treatment concurrently.Before and at 6 and 12 weeks after intervention,a standard respiratory function test,a voice test,the St.George's Respiratory Questionnaire,and a quality of life questionnaire were administered.The results showed that the inspiratory capacity,forced expiratory volume in 1 second,forced vital capacity,maximal mid-expiratory flow rate,sing-loud pressure level,and sustained note length were significantly increased in the intervention group compared with the control group.The St.George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group.These findings suggest that oral motor respiratory exercise and vocal intonation therapy,as respiratory training methods in music therapy,are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2019-78-1)on May 27,2019 and was registered with the Chinese Clinical Trial Registry(registration number:Chi CTR1900026922)on October 26,2019.展开更多
To determine whether olomoucine acts synergistically with bone morphogenetic protein-4 in the treatment of spinal cord injury, we established a rat model of acute spinal cord contusion by impacting the spinal cord at ...To determine whether olomoucine acts synergistically with bone morphogenetic protein-4 in the treatment of spinal cord injury, we established a rat model of acute spinal cord contusion by impacting the spinal cord at the T8 vertebra. We injected a suspension of astrocytes derived from glial-restricted precursor cells exposed to bone morphogenetic protein-4 （GDAsBMP） into the spinal cord around the site of the injury, and/or olomoucine intraperitoneally. Olomoucine effectively inhibited astrocyte proliferation and the formation of scar tissue at the injury site, but did not prevent proliferation of GDAsBMP or inhibit their effects in reducing the spinal cord lesion cavity. Furthermore, while GDAsBMP and olomoucine independently resulted in small improve- ments in locomotor function in injured rats, combined administration of both treatments had a significantly greater effect on the restoration of motor function. These data indicate that the combined use of olomoucine and GDAsBMP creates a better environment for nerve regeneration than the use of either treatment alone, and contributes to spinal cord repair after injury.展开更多
OBJECTIVE： To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES： Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China...OBJECTIVE： To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES： Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms（the Medical Subject Headings） such as ＂myelotomy＂, ＂spinal cord injuries＂, ＂rats＂, ＂randomized controlled trial＂ and all related entry terms were searched. DATA SELECTION： Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software（version 5.3） was used for data processing. The χ^2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES： Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS： Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees（moderate or severe）. The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group（weighted mean difference（WMD） = 0.60; 95% confidence interval（CI）： 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI： 1.56–2.64; P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57; P 〈 0.001; WMD = 1.66; 95% CI： 0.80–2.52; P 〈 0.001; WMD = 2.09; 95% CI： 0.92–3.26, P 〈 0.001; WMD = 2.25; 95% CI： 1.06–3.44, P 〈 0.001）. The overall heterogeneity was high（I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%）. The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group（WMD = 0.91, 95% CI： 0.52–1.3, P 〈 0.001; WMD = 2.10; 95% CI： 1.56–2.64, P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57, P 〈 0.001; WMD = 2.50, 95% CI： 1.72–3.28, P 〈 0.001; WMD = 3.29, 95% CI： 2.21–4.38, P 〈 0.001; WMD = 3.27; 95% CI： 2.31–4.23, P 〈 0.001）. The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury（P = 0.75; P = 0.92）. CONCLUSION： To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.展开更多
The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system ...The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system of patients with disorder of consciousness.Although past studies have recommended that patients with disorder of consciousness listen to patient-preferred music, this practice is not universally accepted by researchers.Twenty patients with severe disorder of consciousness listened to either therapist-selected(n = 10, 6 males and 4 females;43.33 ± 18.76 years old) or patient-preferred(n = 10, 5 males and 5 females, 48.83 ± 18.79 years old) musical therapy, 30 minutes/day, 5 times/week for 6 weeks.The results showed no obvious differences in heart rate variability-related parameters including heart rate, standard deviation of normal-to-normal R-R intervals, and the root-mean-square of successive heartbeat interval differences of successive heartbeat intervals between the two groups of patients.However, percentage of differences exceeding 50 ms between adjacent normal number of intervals, low-frequency power/high-frequency power, high-frequency power norm, low-frequency power norm, and total power were higher in patients receiving therapist-selected music than in patients receiving their own preferred music.In contrast, this relationship was reversed for the high-frequency power and very-low-frequency band.These results suggest that compared with preferred musical stimulation, therapist-selected musical stimulation resulted in higher interactive activity of the autonomic nervous system.Therefore, therapist-selected musical stimulation should be used to arouse the autonomic nervous system of patients with disorder of consciousness.This study was approved by the Institutional Ethics Committee of China Rehabilitation Research Center, China(approval No.2018-022-1) on March 12, 2018 and registered with the Chinese Clinical Trial Registry(registration number Chi CTR1800017809) on August 15, 2018.展开更多
Spinal cord injury (SCI) impairs the au-tonomic nervous system and is associated with dysfunc-tion or failure of multiple organs. Rehabilitation after SCI is a complicated process that involves improvement of motor an...Spinal cord injury (SCI) impairs the au-tonomic nervous system and is associated with dysfunc-tion or failure of multiple organs. Rehabilitation after SCI is a complicated process that involves improvement of motor and sensory function and amelioration of com-plications. Accumulating evidence has demonstrated that melatonin treatment could protect the neural tissues of the spinal cord from secondary injury after SCI. Melatonin is an indoleamine naturally produced by the pineal gland and other tissues. It can easily cross the blood-brain bar-rier and has been shown to have neuroprotective proper-ties in animal models with neurological injury, such as traumatic brain injury and SCI. We reviewed the potential mechanisms of melatonin treatment reducing SCI-relat-ed complications such as disruption of microcirculation, neurogenic bowel dysfunction, and circadian disorders.展开更多
Diffusion tensor imaging(DTI)technique can detect the dispersion of water molecules in the white matter of the spinal cord,the integrity of the spinal fiber bundle,and the pathological changes after injury.Clinically,...Diffusion tensor imaging(DTI)technique can detect the dispersion of water molecules in the white matter of the spinal cord,the integrity of the spinal fiber bundle,and the pathological changes after injury.Clinically,DTI is sensitive to acute and chronic spinal cord injuries,and is most commonly used for the diagnosis of cervical spondylotic myelopathy,multiple sclerosis,secondary brain damage after spinal cord injury,and spinal nerve root damage.In animal studies involving rats,monkeys,cattle,cats,pigs,dogs,etc.,DTI could quantitatively analyze the microstructural and pathological changes of the injured spinal cord and provide a powerful auxiliary diagnosis for behavioral evaluation.展开更多
Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cle...Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.展开更多
Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Seleniu...Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.展开更多
Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure ...Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I(steep rise) 1–7 hours, stage Ⅱ(steady rise) 8–38 hours, and stage Ⅲ(descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages Ⅱ and Ⅲ of spinal cord injury.展开更多
Pudendal nerve plays an important role in urine storage and voiding.Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury...Pudendal nerve plays an important role in urine storage and voiding.Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury.We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve.This study explored the excitatory pudendal-to-bladder reflex in beagle dogs,with intact or injured spinal cord,by electrical stimulation of the pudendal nerve trunk.The optimal stimulation frequency was approximately 15–25 Hz.This excitatory effect was dependent to some extent on the bladder volume.We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Neurogenic bladder （ NB） dysfunction caused by spinal cord injury （ SCI ） or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include ...Neurogenic bladder （ NB） dysfunction caused by spinal cord injury （ SCI ） or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include medication, injection of Botulinum toxin A into the detrusor, neuromodulation and surgery. There are also emerging approaches, such as tissue engineering, stem cell transplantation and gene therapy. In recent years, we have carried out explorations in both therapeutic areas and tried to translate basic research into clinical practice. This paper reviews our work in this regard, and provides references for future research.展开更多
Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reper...Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reperfusion injury is likely to occur and often results in neurological dysfunction.Apart from motor and speech impediments,patients with such injury may also suffer from impaired higher-level cognitive functions such as learning and memory,placing a heavy burden on families and society.Brain areas associated with the limbic system include the hippocampus,corpus striatum,and amygdala,which are linked with cognitive function.Those brain regions are easily damaged by hypoxia,and since they are connected with the dopaminergic pathway,global cerebral ischemia–reperfusion can damage the dopaminergic pathway as well and affect the projection of dopaminergic neurons in the limbic system.This review article examines the feasibility of using dopamine,a neurotransmitter heavily involved in cognitive function,in experimental research and clinical treatment of global cerebral ischemia–reperfusion injury.Specifically,we examine the effects of dopamine on post-injury cognition and neuronal plasticity,with the ultimate goal of identifying a new tool for clinical treatment.展开更多
The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific challenge.Astrocytes are an essential component of the CNS and participate in many physiolog...The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific challenge.Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation,axon growth regulation,neuronal support,and higher cognitive functions such as memory.Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons.Building on in vitro work,many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells.However,many findings in this field are controversial,as the source of new neurons has been questioned.This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury,brain injury,Huntington’s disease,Parkinson’s disease,Alzheimer’s disease,and other neurodegenerative conditions.展开更多
Oligodendrocyte progenitor cells(OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic...Oligodendrocyte progenitor cells(OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic stem cells(hESCs) or neural stem cells(NSCs) as starter cell sources for the differentiation process. However, NSCs are restricted in availability and the present method for generation of oligodendrocytes(OLs) from ESCs often requires a lengthy period of time. Here, we demonstrated a protocol to efficiently derive OPCs from human induced pluripotent stem cells(hiPSCs) by forced expression of two transcription factors(2TFs), Sox10 and Olig2. With this method, PDGFRα+ OPCs can be obtained in 14 days and O4^+ OPCs in 56 days.Furthermore, OPCs may be able to differentiate to mature OLs that could ensheath axons when co-cultured with rat cortical neurons. The results have implications in the development of autologous cell therapies.展开更多
Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor n...Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.展开更多
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
基金supported by Scientific Research Project of Establishment of the Winter Olympics Sports Injury Rehabilitation Diagnosis and Treatment System and Green Channel Demonstration of China,No.2018YFF0301104(to JJL)China Rehabilitation Science Institute,No.2020cz-10(to WZW)Scientific Research Foundation of China Rehabilitation Research Center,No.2017zx-32(to XYZ)。
文摘In previous studies,researchers have used singing to treat respiratory function in patients with spinal cord injury.However,few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury.Vocal respiratory training(VRT)is a type of vocal muscle-related treatment that is often a component of music therapy(MT)and focuses on strengthening respiratory muscles and improving lung function.In this randomized controlled study,we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury.Of an initial group of 37 patients,26 completed the music therapy intervention,which comprised five 30-minute sessions per week for 12 weeks.The intervention group(n=13)received VRT training delivered by professional certified music therapists.The control group(n=13)received respiratory physical therapy delivered by professional physical therapists.Compared with the control group,we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention.Further,the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification,with an increased number,path length,thickness,and density of nerve fiber bundles.These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2020-013-1)on April 1,2020,and was registered with the Chinese Clinical Trial Registry(registration No.Chi CTR2000037871)on September 2,2020.
基金supported by the National Natural Science Foundation of China,Nos.82071400,81870979the Scientific Research Foundation of China Rehabilitation Research Center,No.2020cz-01the Special Capital Health Research and Development of China,No.2018-1-6011(all to JJL)。
文摘Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.
基金supported by the National Natural Science Foundation of China,No.81272164the Special Fund for Basic Scientific Research of Central Public Research Institutes in China,No.2015CZ-6,2016CZ-4+2 种基金the Beijing Institute for Brain Disorders in China,No.201601,0000-100031the Supporting Program of the “Twelve Five-year Plan” for Science&Technology Research of China,No.2012BAI34B02a grant from the Ministry of Science and Technology of China,No.2015CB351701
文摘Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T_（10） spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord（R = 0.919, P = 0.027）, white matter（R = 0.932, P = 0.021）, and gray matter（R = 0.882, P = 0.048）. Additionally, the other parameters had almost no correlation with the score（P 〉 0.05）. In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.
基金Scientific Research Foundation of China Rehabilitation Research Center,No.2019zx-23(to SHL)the Natural Science Foundation of Beijing of China,No.7192238。
文摘Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury.Among 31 included patients with spinal cord injury,18 completed the treatment.These 18 patients were randomly assigned to undergo music therapy(intervention group,30 min/d,5 times a week,for a total of 12 weeks;n=9,7 males and 2 females;30.33±11.74 years old)or normal respiratory training(control group,n=9;8 males and 1 female;34.78±11.13 years old).Both patient groups received routine treatment concurrently.Before and at 6 and 12 weeks after intervention,a standard respiratory function test,a voice test,the St.George's Respiratory Questionnaire,and a quality of life questionnaire were administered.The results showed that the inspiratory capacity,forced expiratory volume in 1 second,forced vital capacity,maximal mid-expiratory flow rate,sing-loud pressure level,and sustained note length were significantly increased in the intervention group compared with the control group.The St.George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group.These findings suggest that oral motor respiratory exercise and vocal intonation therapy,as respiratory training methods in music therapy,are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2019-78-1)on May 27,2019 and was registered with the Chinese Clinical Trial Registry(registration number:Chi CTR1900026922)on October 26,2019.
基金supported by a grant from the ‘Twelve Five-year Plan’ for Science & Technology Research of China,No.2012BAI34B02
文摘To determine whether olomoucine acts synergistically with bone morphogenetic protein-4 in the treatment of spinal cord injury, we established a rat model of acute spinal cord contusion by impacting the spinal cord at the T8 vertebra. We injected a suspension of astrocytes derived from glial-restricted precursor cells exposed to bone morphogenetic protein-4 （GDAsBMP） into the spinal cord around the site of the injury, and/or olomoucine intraperitoneally. Olomoucine effectively inhibited astrocyte proliferation and the formation of scar tissue at the injury site, but did not prevent proliferation of GDAsBMP or inhibit their effects in reducing the spinal cord lesion cavity. Furthermore, while GDAsBMP and olomoucine independently resulted in small improve- ments in locomotor function in injured rats, combined administration of both treatments had a significantly greater effect on the restoration of motor function. These data indicate that the combined use of olomoucine and GDAsBMP creates a better environment for nerve regeneration than the use of either treatment alone, and contributes to spinal cord repair after injury.
基金supported by the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2015CZ-6,2016CZ-4a grant from the Beijing Institute for Brain Disorders,No.201601
文摘OBJECTIVE： To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES： Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms（the Medical Subject Headings） such as ＂myelotomy＂, ＂spinal cord injuries＂, ＂rats＂, ＂randomized controlled trial＂ and all related entry terms were searched. DATA SELECTION： Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software（version 5.3） was used for data processing. The χ^2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES： Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS： Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees（moderate or severe）. The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group（weighted mean difference（WMD） = 0.60; 95% confidence interval（CI）： 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI： 1.56–2.64; P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57; P 〈 0.001; WMD = 1.66; 95% CI： 0.80–2.52; P 〈 0.001; WMD = 2.09; 95% CI： 0.92–3.26, P 〈 0.001; WMD = 2.25; 95% CI： 1.06–3.44, P 〈 0.001）. The overall heterogeneity was high（I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%）. The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group（WMD = 0.91, 95% CI： 0.52–1.3, P 〈 0.001; WMD = 2.10; 95% CI： 1.56–2.64, P 〈 0.001; WMD = 2.65; 95% CI： 1.73–3.57, P 〈 0.001; WMD = 2.50, 95% CI： 1.72–3.28, P 〈 0.001; WMD = 3.29, 95% CI： 2.21–4.38, P 〈 0.001; WMD = 3.27; 95% CI： 2.31–4.23, P 〈 0.001）. The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury（P = 0.75; P = 0.92）. CONCLUSION： To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.
基金supported by the Beijing Science and Technology Project Foundation of China, No.Z181100001718066(to HTL)。
文摘The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system of patients with disorder of consciousness.Although past studies have recommended that patients with disorder of consciousness listen to patient-preferred music, this practice is not universally accepted by researchers.Twenty patients with severe disorder of consciousness listened to either therapist-selected(n = 10, 6 males and 4 females;43.33 ± 18.76 years old) or patient-preferred(n = 10, 5 males and 5 females, 48.83 ± 18.79 years old) musical therapy, 30 minutes/day, 5 times/week for 6 weeks.The results showed no obvious differences in heart rate variability-related parameters including heart rate, standard deviation of normal-to-normal R-R intervals, and the root-mean-square of successive heartbeat interval differences of successive heartbeat intervals between the two groups of patients.However, percentage of differences exceeding 50 ms between adjacent normal number of intervals, low-frequency power/high-frequency power, high-frequency power norm, low-frequency power norm, and total power were higher in patients receiving therapist-selected music than in patients receiving their own preferred music.In contrast, this relationship was reversed for the high-frequency power and very-low-frequency band.These results suggest that compared with preferred musical stimulation, therapist-selected musical stimulation resulted in higher interactive activity of the autonomic nervous system.Therefore, therapist-selected musical stimulation should be used to arouse the autonomic nervous system of patients with disorder of consciousness.This study was approved by the Institutional Ethics Committee of China Rehabilitation Research Center, China(approval No.2018-022-1) on March 12, 2018 and registered with the Chinese Clinical Trial Registry(registration number Chi CTR1800017809) on August 15, 2018.
文摘Spinal cord injury (SCI) impairs the au-tonomic nervous system and is associated with dysfunc-tion or failure of multiple organs. Rehabilitation after SCI is a complicated process that involves improvement of motor and sensory function and amelioration of com-plications. Accumulating evidence has demonstrated that melatonin treatment could protect the neural tissues of the spinal cord from secondary injury after SCI. Melatonin is an indoleamine naturally produced by the pineal gland and other tissues. It can easily cross the blood-brain bar-rier and has been shown to have neuroprotective proper-ties in animal models with neurological injury, such as traumatic brain injury and SCI. We reviewed the potential mechanisms of melatonin treatment reducing SCI-relat-ed complications such as disruption of microcirculation, neurogenic bowel dysfunction, and circadian disorders.
文摘Diffusion tensor imaging(DTI)technique can detect the dispersion of water molecules in the white matter of the spinal cord,the integrity of the spinal fiber bundle,and the pathological changes after injury.Clinically,DTI is sensitive to acute and chronic spinal cord injuries,and is most commonly used for the diagnosis of cervical spondylotic myelopathy,multiple sclerosis,secondary brain damage after spinal cord injury,and spinal nerve root damage.In animal studies involving rats,monkeys,cattle,cats,pigs,dogs,etc.,DTI could quantitatively analyze the microstructural and pathological changes of the injured spinal cord and provide a powerful auxiliary diagnosis for behavioral evaluation.
基金supported by the National Natural Science Foundation of China,No.81870979(to JJL),No.81271366(to MLY)the National Key R&D Program of China,No.2018YFF0301104(to JJL)+4 种基金the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2018CZ-1(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2018ZX-30(to FG)the Scientific Research Foundation of CRRC,No.2012C-1(to JJL)the Major Science and Technology Project of Beijing of China,No.D161100002816004(to JJL)the Special Capital Health Research and Development of China,No.2018-1-6011(to JJL)
文摘Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.
基金supported by the National Natural Science Foundation of China, No.81870979(to JJL)the Scientific Research Foundation of China Rehabilitation Research Center, No.2020-02(to JJL)the Natural Science Foundation of Changsha, No.kq2014285(to YXC)
文摘Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.
基金supported by the National Natural Science Foundation of China,No.81272164(to JJL)the Special Fund for Basic Scientific Research of Central Public Research Institutes in China,No.2016CZ-4(to JJL),2018CZ-1(to JJL)+1 种基金the Beijing Institute for Brain Disorders in China,No.0000-100031(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2017ZX-22,2017ZX-20(to JJL)
文摘Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I(steep rise) 1–7 hours, stage Ⅱ(steady rise) 8–38 hours, and stage Ⅲ(descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages Ⅱ and Ⅲ of spinal cord injury.
基金supported by the Capital Medical Development Research Fund of China,No.2014-2-4141
文摘Pudendal nerve plays an important role in urine storage and voiding.Our hypothesis is that a neuroprosthetic device placed in the pudendal nerve trunk can modulate bladder function after suprasacral spinal cord injury.We had confirmed the inhibitory pudendal-to-bladder reflex by stimulating either the branch or the trunk of the pudendal nerve.This study explored the excitatory pudendal-to-bladder reflex in beagle dogs,with intact or injured spinal cord,by electrical stimulation of the pudendal nerve trunk.The optimal stimulation frequency was approximately 15–25 Hz.This excitatory effect was dependent to some extent on the bladder volume.We conclude that stimulation of the pudendal nerve trunk is a promising method to modulate bladder function.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
文摘Neurogenic bladder （ NB） dysfunction caused by spinal cord injury （ SCI ） or diseases of the central nervous system or peripheral nerves is a major medical and social problem. Traditional treatments to NB include medication, injection of Botulinum toxin A into the detrusor, neuromodulation and surgery. There are also emerging approaches, such as tissue engineering, stem cell transplantation and gene therapy. In recent years, we have carried out explorations in both therapeutic areas and tried to translate basic research into clinical practice. This paper reviews our work in this regard, and provides references for future research.
基金This study was supported by the National Natural Science Foundation of China(grant number:81100982)Central Public-Interest Scientific Institution Basal Research Fund(grant number:2018CZ-5).
文摘Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reperfusion injury is likely to occur and often results in neurological dysfunction.Apart from motor and speech impediments,patients with such injury may also suffer from impaired higher-level cognitive functions such as learning and memory,placing a heavy burden on families and society.Brain areas associated with the limbic system include the hippocampus,corpus striatum,and amygdala,which are linked with cognitive function.Those brain regions are easily damaged by hypoxia,and since they are connected with the dopaminergic pathway,global cerebral ischemia–reperfusion can damage the dopaminergic pathway as well and affect the projection of dopaminergic neurons in the limbic system.This review article examines the feasibility of using dopamine,a neurotransmitter heavily involved in cognitive function,in experimental research and clinical treatment of global cerebral ischemia–reperfusion injury.Specifically,we examine the effects of dopamine on post-injury cognition and neuronal plasticity,with the ultimate goal of identifying a new tool for clinical treatment.
基金supported by the National Natural Science Foundation of China,No.82071214(to JJL)Basic Scientific Research of the Central Public Research Institutes in China,No.2021CZ-2(to JJL)Special Fund for Joint Training of Doctoral Students between University of Health and Rehabilitation Sciences and China Rehabilitation Research Center,No.2020kfdx-009(to JJL and ZT)。
文摘The inability of damaged neurons to regenerate within the mature central nervous system(CNS)is a significant neuroscientific challenge.Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation,axon growth regulation,neuronal support,and higher cognitive functions such as memory.Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons.Building on in vitro work,many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells.However,many findings in this field are controversial,as the source of new neurons has been questioned.This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury,brain injury,Huntington’s disease,Parkinson’s disease,Alzheimer’s disease,and other neurodegenerative conditions.
基金supported by the Stem Cell and Translation National Key Project(2016ZY05002449)National Basic Research Program of China(2011CB965103,2012CBA01307)+2 种基金National Natural Science Foundation of China(81661130160,81422014,81561138004)Beijing Municipal Natural Science Foundation(5142005)Royal Society-Newton Advanced Fellowship(NA150482)
文摘Oligodendrocyte progenitor cells(OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic stem cells(hESCs) or neural stem cells(NSCs) as starter cell sources for the differentiation process. However, NSCs are restricted in availability and the present method for generation of oligodendrocytes(OLs) from ESCs often requires a lengthy period of time. Here, we demonstrated a protocol to efficiently derive OPCs from human induced pluripotent stem cells(hiPSCs) by forced expression of two transcription factors(2TFs), Sox10 and Olig2. With this method, PDGFRα+ OPCs can be obtained in 14 days and O4^+ OPCs in 56 days.Furthermore, OPCs may be able to differentiate to mature OLs that could ensheath axons when co-cultured with rat cortical neurons. The results have implications in the development of autologous cell therapies.
基金supported by the Stem Cell and Translation National Key Project(No.2016YFA0101403,to ZC)the National Natural Science Foundation of China(Nos.81973351,81661130160,81422014,81561138004,all to ZC)+7 种基金the Beijing Municipal Natural Science Foundation(No.5142005,to ZC)Beijing Talents Foundation(No.2017000021223TD03,to ZC)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-Year Plan(No.CIT&TCD20180333,to ZC)the Beijing Medical System High Level Talent Award(No.2015-3-063,to ZC)Beijing Municipal Health Commission Fund(No.PXM2020_026283_000005)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund(No.2018A03,to ZC)the Royal Society-Newton Advanced Fellowship(No.NA150482,to ZC)the USA Veterans Administration(No.I01 RX002264-01A2,to PL).
文摘Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the UK.The loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the disease.Although there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron degeneration.Thus,there is still a lack of effective treatment for this debilitating neurodegenerative disorder.Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons.Stem cell therapies may also be able to re-establish the motor control of voluntary muscles.Here,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis.We focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem cells.In our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord.Furthermore,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety of stem cell derivatives,including induced pluripotent stem cells,are being considered for clinical trials for various diseases.
